Interleukin-10 (IL-10) is one of the cytokines implicated in the pathogenesis of diffuse large B-cell lymphoma (DLBCL) in which it acts as auto/paracrine growth factor for lymphoma growth.
Carriage of two copies of the 'low IL10' haplotype rs1800896_A/rs1800871_T/rs1800872_A was associated with decreased lymphoma risk that varied by number of copies (Ptrend = 0.02).
Even small numbers of adoptively transferred B10 cells dramatically suppressed CD20 mAb-mediated lymphoma depletion by inhibiting mAb-mediated monocyte activation and effector function through IL-10-dependent mechanisms.
Five hundred patients with aggressive NHL treated with CHOP/CHOEP were analyzed for IL-10 gene polymorphisms, including distal loci -7400InDel, -6752AT (rs6676671), and -6208CG (rs10494879) in comparison with proximal loci -3538AT (rs1800890), -1087AG (rs1800896), and -597AC (rs1800872) according to the incidence and outcome of the lymphoma.
Here, we report that myeloid-deficient Becn1 (Becn1ΔM) mice developed neutrophilia, were hypersusceptible to LPS-induced septic shock, and had a high risk of developing spontaneous precursor B cell (pre-B cell) lymphoma with elevated expression of immunosuppressive molecules programmed death ligand 1 (PD-L1) and IL-10.
In addition, polymorphisms in the interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta) genes previously associated with lymphoma development were also typed.
In an independent genetic analysis of single-nucleotide polymorphisms within the promoter region of the IL10 gene in 1157 MACS subjects, a high IL10-expressing genotype (-592 C/C) was overrepresented among lymphoma subjects (P = 0.009), even when controlling for race (P = 0.006).
Interestingly, several B lymphoma cell lines were observed to secrete 400-1300 pg/ml IL-10 in vitro, and coculture of human macrophages with lymphoma conditioned medium increased significantly their phagocytic capacity.
Our results suggest that IL-10 and IL-13 contribute to the pathogenesis of PSS and might explain the B cell abnormalities and the development of lymphoma observed in this autoimmune disease.
Qualitative and quantitative expression of EBV Encoded RNAs (EBER1, EBER2) and anti-inflammatory cytokine (interleukin-10) in FFPE EBV positive lymphoma tissue samples were then analysed by using reverse transcriptase polymerase chain reaction (RT-PCR) and real time polymerase chain reaction (qRT-PCR), respectively.
Since murine Ly1-positive peritoneal or lymphoma B cells strongly express IL-10, we examined malignant cells from patients with acute and chronic leukemias by reverse transcriptase polymerase chain reaction (RT-PCR) for the expression of IL-10 mRNA.
These results identify CXCL13 and IL-10 as potentially important biomarkers of CNS lymphoma that merit further evaluation and support incorporation of CXCL13 and IL-10 into diagnostic algorithms for the workup of focal brain lesions in which lymphoma is a consideration.
Thus, polymorphisms in the IL-10 gene promoter which are associated with a low IL-10 producing phenotype may influence susceptibility to aggressive forms of lymphoma or may contribute to the pathogenesis of this disease.
With limited sample size, gradient boosting can differentiate endophthalmitis from uveitis and lymphoma by IL-6 and IL-10 with high sensitivity and specificity; however, a larger cohort is needed for further validation.